P382: A CLINICAL PROGNOSTIC SCORING SYSTEM FOR ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION OUTCOMES IN ADULT PATIENTS WITH PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKAEMIA
Authors: Song Wang, Jianying Zhou, Xiao-Lu Zhu, Hai-Xia Fu, Ling-Ling Shi, Yun He, Feng-Rong Wang, Yuan-Yuan Zhang, Xiao-Dong Mo, Chen-Hua Yan, Yuan Kong, Wei Han, Jing-Zhi Wang, Yu Wang, Huan Chen, Yu-Hong Chen, Xiang-Yu Zhao, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: HemaSphere (2023)

Background: As the most common cytogenetic abnormality in acute lymphoblastic leukaemia (ALL), the Philadelphia chromosome (Ph) is significantly associated with poor survival. Allogeneic haematopoietic stem cell transplantation (HSCT), a curative therapy, remains an important treatment for Ph+ ALL. It is critical to distinguish Ph+ ALL patients with a high risk of death to provide specific therapeutic management and improve their overall survival. Considering the rarity of adult ALL, however, an effective and feasible clinical scoring system for adult Ph+ ALL patients is lacking. Aims: To establish a clinical prognostic scoring system for selecting post-transplant adult Ph+ ALL patients with a higher risk of death Methods: The data from 751 adult Ph+ ALL patients who underwent allo-HSCT at Peking University People’s Hospital between 2010 and 2022 were retrospectively analysed and further randomly divided into 1) a derivation (60%) cohort of 451 patients and 2) a validation (40%) cohort of 200 patients. We used a final Cox proportional hazards regression model to determine the prognostic factors for OS in adult Ph+ ALL patients. The prognostic model performance was assessed by evaluating the discrimination [area under the curve (AUC)], calibration (calibration plot), and net benefit [decision curve analysis (DCA)] Results: Between January 2010 and August 2022, 751 of 2642 ALL patients (28.4%) were diagnosed with adult Ph+ ALL. Among them, 169 patients (22.5%) died, and 171 patients (22.7%) relapsed. Through multivariable Cox proportional hazards regression, seven prognosis risk factors were selected, including anaemia (Hb＜120 g/L) at diagnosis (OR,1.83; 95% CI, 1.12-3.00), central nervous system (CNS) involvement before HSCT (OR, 2.13; 95% CI, 1.12-4.08), age≥30 at HSCT (OR, 1.83; 95% CI, 1.12-3.00), remission condition≥CR1 (CRn or NR) at HSCT (OR, 1.79; 95% CI, 0.97-3.32), BCR-ABL/ABL>1% at HSCT (OR, 1.88; 95% CI, 1.07-3.30), having severe graft-versus-host disease (including≥Grade 3 aGVHD and extensive cGVHD) (OR, 2.53; 95% CI, 1.50-4.27) and thrombocytopenia after HSCT (OR, 6.47; 95% CI, 4.06-10.30). Hence, a prognostic model was established to predict 5-year overall survival, which was named ABSTRAC (age, BCR-ABL, severe GVHD, thrombocytopenia, remission, anaemia, and CNS involvement). According to the regression coefficient, 2 scores were assigned for thrombocytopenia after HSCT, and other factors were each given 1 point. The patients were stratified into 3 risk groups: low risk (0-1), intermediate risk (2-3), and high risk (≥4), which showed 5-year survival rates of 94.1% for low risk, 66.4% for intermediate risk, and 29.3% for high risk (P<.001). The AUC of the prognostic scoring model was 0.829 (0.760-0.897) for the validation cohort. The calibration plots showed high consistency between the predicted and observed outcomes. The decision curve analysis indicated that adult Ph+ ALL patients could benefit from this prognostic model. We also found that platelets≤72×109/L at diagnosis (OR, 2.54; 95% CI, 1.28-5.05), CNS involvement before HSCT (OR, 2.77; 95% CI, 1.14-6.73), ABL kinase domain mutations (OR, 6.57; 95% CI, 2.91-14.81), cGVHD (OR, 2.35; 95% CI, 1.36-4.07) and without aGVHD (OR, 1.84; 95% CI, 1.12-3.03) are the risk factors for relapse Summary/Conclusion: We explored the ABSTRAC clinical prognostic scoring system to predict 5-year overall survival in adult Ph+ALL patients after allo-HSCT, which can identify adult Ph+ ALL patients with a high risk of death and aid in clinical decision-making and treatment. Keywords: Survival, Prognostic, Allogeneic hematopoietic stem cell transplant, Ph+ ALL